Premium
cAMP ‐induced activation of protein kinase A and p190B Rho GAP mediates down‐regulation of TC 10 activity at the plasma membrane and neurite outgrowth
Author(s) -
Koinuma Shingo,
Takeuchi Kohei,
Wada Naoyuki,
Nakamura Takeshi
Publication year - 2017
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12538
Subject(s) - neurite , rhoa , rac1 , microbiology and biotechnology , biology , gtpase , small gtpase , pak1 , protein kinase a , signal transduction , kinase , biochemistry , in vitro
Cyclic AMP plays a pivotal role in neurite growth. During outgrowth, a trafficking system supplies membrane at growth cones. However, the cAMP ‐induced signaling leading to the regulation of membrane trafficking remains unknown. TC 10 is a Rho family GTP ase that is essential for specific types of vesicular trafficking. Recent studies have shown a role of TC 10 in neurite growth in NGF ‐treated PC 12 cells. Here, we investigated a mechanical linkage between cAMP and TC 10 in neuritogenesis. Plasmalemmal TC 10 activity decreased abruptly after cAMP addition in neuronal cells. TC 10 was locally inactivated at extending neurite tips in cAMP ‐treated PC 12 cells. TC 10 depletion led to a decrease in cAMP ‐induced neurite outgrowth. Constitutively active TC 10 could not rescue this growth reduction, supporting our model for a role of GTP hydrolysis of TC 10 in neuritogenesis by accelerating vesicle fusion. The cAMP ‐induced TC 10 inactivation was mediated by PKA . Considering cAMP ‐induced RhoA inactivation, we found that p190B, but not p190A, mediated inactivation of TC 10 and RhoA. Upon cAMP treatment, p190B was recruited to the plasma membrane. STEF depletion and Rac1‐N17 expression reduced cAMP ‐induced TC 10 inactivation. Together, the PKA ‐ STEF ‐Rac1‐p190B pathway leading to inactivation of TC 10 and RhoA at the plasma membrane plays an important role in cAMP ‐induced neurite outgrowth.